RESUMO
De novo variants affecting monoubiquitylation of histone H2B (H2Bub1) are enriched in human congenital heart disease. H2Bub1 is required in stem cell differentiation, cilia function, post-natal cardiomyocyte maturation and transcriptional elongation. However, how H2Bub1 affects cardiogenesis is unknown. We show that the H2Bub1-deposition complex (RNF20-RNF40-UBE2B) is required for mouse cardiogenesis and for differentiation of human iPSCs into cardiomyocytes. Mice with cardiac-specific Rnf20 deletion are embryonic lethal and have abnormal myocardium. We then analyzed H2Bub1 marks during differentiation of human iPSCs into cardiomyocytes. H2Bub1 is erased from most genes at the transition from cardiac mesoderm to cardiac progenitor cells but is preserved on a subset of long cardiac-specific genes. When H2Bub1 is reduced in iPSC-derived cardiomyocytes, long cardiac-specific genes have fewer full-length transcripts. This correlates with H2Bub1 accumulation near the center of these genes. H2Bub1 accumulation near the center of tissue-specific genes was also observed in embryonic fibroblasts and fetal osteoblasts. In summary, we show that normal H2Bub1 distribution is required for cardiogenesis and cardiomyocyte differentiation, and suggest that H2Bub1 regulates tissue-specific gene expression by increasing the amount of full-length transcripts.
Assuntos
Cardiopatias Congênitas , Histonas , Ubiquitina-Proteína Ligases , Animais , Humanos , Camundongos , Coração/embriologia , Histonas/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Ubiquitina-Proteína Ligases/metabolismo , UbiquitinaçãoRESUMO
AbstractThe American Urological Association (AUA) and American College of Surgeons (ACS) codes of professionalism require surgeons to disclose the specific roles and responsibilities of trainees to patients during the informed consent process. The objective of this study is to analyze how these requirements are met by urology training programs. An anonymous electronic survey was distributed to the program directors (PDs) of the 143 Accreditation Council for Graduate Medical Education urology residency programs in the United States in 2021. Information was collected regarding program demographics, aspects of the program's consent process, and the disclosure to patients of the role and participation of residents in their surgery. There were 49 responses to the survey (34.3% response rate). Nearly 70 percent of PDs reported that attending physicians lead the consent process. The topics covered during consent discussion include possible complications (25%), expected recovery time (23%), length of the surgery (22%), the people involved (18%), and their specific roles (7%). Many PDs do not explicitly discuss trainee involvement (48.8%) or when a resident is to perform the majority of the case (87.8%). The majority of PDs (78.8%) communicate medical student involvement, but 73.2 percent reported having a patient decline participation of a trainee after describing their role. Despite the AUA and ACS codes of professionalism, many urologists do not disclose resident involvement in surgery to patients. Further discussions are needed to explore how to better balance resident education and patient autonomy.
Assuntos
Internato e Residência , Urologia , Humanos , Estados Unidos , Educação de Pós-Graduação em Medicina , Inquéritos e Questionários , Consentimento Livre e EsclarecidoRESUMO
The multidisciplinary nature of artificial intelligence (AI) has allowed for rapid growth of its application in medical imaging. Artificial intelligence algorithms can augment various imaging modalities, such as X-rays, CT, and MRI, to improve image quality and generate high-resolution three-dimensional images. AI reconstruction of three-dimensional models of patient anatomy from CT or MRI scans can better enable urologists to visualize structures and accurately plan surgical approaches. AI can also be optimized to create virtual reality simulations of surgical procedures based on patient-specific data, giving urologists more hands-on experience and preparation. Recent development of artificial intelligence modalities, such as TeraRecon and Ceevra, offer rapid and efficient medical imaging analyses aimed at enhancing the provision of urologic care, notably for intraoperative guidance during robot-assisted radical prostatectomy (RARP) and partial nephrectomy.
Assuntos
Inteligência Artificial , Procedimentos Cirúrgicos Urológicos , Humanos , Procedimentos Cirúrgicos Urológicos/métodos , Medicina de Precisão/métodos , Urologia/métodos , Diagnóstico por Imagem/métodos , Procedimentos Cirúrgicos Robóticos/métodosRESUMO
OBJECTIVE: To determine the characteristics of US medical schools associated with successful urology match applicants. MATERIALS AND METHODS: Using publicly available data, demographics and bibliometrics were collected for 1814 current urology residents who attend a US-based Accreditation Council for Graduate Medical Education (ACGME) Accredited program, reflecting matched applicants over a 6-year period from 2016-2021. A generated list of US feeder medical schools for urology was analyzed for correlative and predictive factors. Statistical analyses to characterize these factors included Pearson's Correlation Coefficient (PCC) and univariable and multivariable linear regression, respectively, as needed. RESULTS: There were 516 (28.45%) female residents and 58 (3.20%) international medical graduates. The mean number of published papers and abstracts ± SD pre-residency was 5.54 ± 7.20 with a mean h-index of 1.97 ± 2.24. The Cleveland Clinic Lerner College of Medicine had the highest percentage of successful matches into urology (nâ¯=â¯7, 3.65%), while the State University of New York Downstate Medical Center College of Medicine produced the highest absolute number (nâ¯=â¯41, 3.30%). The presence of a home urology program and pre-residency h-index had the strongest correlation with producing urology residents (PCCâ¯=â¯0.5769 and 0.3709, respectively, P<.0001). CONCLUSION: Understanding the characteristics of a successful urology match applicant and the medical schools that produce them will be vital as USMLE Step 1 exam becomes pass/fail. Further research into these schools' curricula is required to better understand the effect of early exposure to urology on matching into urology.
Assuntos
Internato e Residência , Urologia , Humanos , Feminino , Estados Unidos , Masculino , Urologia/educação , Faculdades de Medicina , Educação de Pós-Graduação em Medicina , AcreditaçãoRESUMO
Treatment of metastatic renal cell carcinoma (mRCC) has evolved with the development of a variety of systemic agents; however, these therapies alone rarely lead to a complete response. Complete consolidative surgery with surgical metastasectomy has been associated with improved survival outcomes in well-selected patients in previous reports. No randomized control trial exists to determine the effectiveness of metastasectomy. Therefore, reviewing observational studies is important to best determine which patients are most appropriate for metastasectomy for mRCC and if such treatment continues to be effective with the development of new systemic therapies such as immunotherapy. In this narrative review, we discuss the indications for metastasectomies, outcomes, factors associated with improved survival, and special considerations such as location of metastasis, number of metastases, synchronous metastases, and use of systemic therapy. Additionally, alternative treatment options and trials involving metastasectomy will be reviewed.